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Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)

Primary Purpose

Refractory Large B-cell Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Axicabtagene Ciloleucel
Rituximab
Fludarabine
Cyclophosphamide
Sponsored by
Kite, A Gilead Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Large B-cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Histologically confirmed large B-cell lymphoma

  • Chemotherapy-refractory disease, defined as one or more of the following:

    • No response to first-line therapy (primary refractory disease)
    • No response to second or greater lines of therapy OR
    • Refractory after autologous stem cell transplant (ASCT)
  • At least 1 measureable lesion according to the Lugano Classification (Cheson 2014).

  • Individuals must have received adequate prior therapy, including at a minimum:

    • Anti-CD20 monoclonal antibody
    • An anthracycline-containing chemotherapy regimen
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria:

  • Known CD19 negative or CD20 negative tumor
  • History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL)
  • Prior CAR therapy or other genetically modified T-cell therapy
  • Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
  • Prior CD19 targeted therapy
  • Clinically significant infection or cardiopulmonary disease
  • Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed)
  • History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases
  • History of autoimmune disease
  • History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

  • Banner MD Anderson Cancer Center
  • City of Hope National Medical Center
  • Stanford Cancer Institute
  • UCLA Hematology/Oncology
  • Mayo Clinic Florida
  • University of Chicago Medical Center
  • Loyola University Medical Center
  • Mayo Clinic
  • John Theurer Cancer Center at Hackensack University Medical Center
  • Columbia University Medical Center, New York Presbyterian Hospital
  • Vanderbilt University Medical Center
  • St. David's South Austin Medical Center
  • The University of Texas MD Anderson Cancer Center
  • Swedish Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Axicabtagene Ciloleucel and Rituximab Combination

Arm Description

Participants will receive rituximab, and fludarabine and cyclophosphamide conditioning chemotherapy, followed by axicabtagene ciloleucel and additional rituximab.

Outcomes

Primary Outcome Measures

Complete Response (CR) Rate
CR rate is defined as the incidence of a CR per the Lugano Classification as determined by study investigators.

Secondary Outcome Measures

Percentage of Participants Experiencing Adverse Events and Clinically Significant Changes in Safety Lab Values
Objective Response Rate (ORR)
ORR is defined as the incidence of either a CR or a partial response (PR) per the Lugano Classification as determined by study investigators.
Duration of Response (DOR)
DOR is defined only for participants who experience an objective response and is the time from the first objective response to disease progression per the Lugano Classification as determined by study investigators or death from any cause.
Progression-Free Survival (PFS)
PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano Classification as determined by study investigators or death from any cause.
Overall Survival (OS)
OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
Levels of Axicabtagene Ciloleucel in Blood

Full Information

First Posted
June 27, 2019
Last Updated
February 10, 2023
Sponsor
Kite, A Gilead Company
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1. Study Identification

Unique Protocol Identification Number
NCT04002401
Brief Title
Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma
Acronym
ZUMA-14
Official Title
A Phase 2 Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
November 5, 2019 (Actual)
Primary Completion Date
January 30, 2023 (Actual)
Study Completion Date
January 30, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kite, A Gilead Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.
Detailed Description
Following at least 24 months of assessments after axicabtagene ciloleucel infusion, participants will be asked to rollover to a separate long-term follow-up study (Study KT-US-982-5968). Participants will complete the remainder of the 15-year follow-up assessments in the KT-US-982-5968 study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Large B-cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Axicabtagene Ciloleucel and Rituximab Combination
Arm Type
Experimental
Arm Description
Participants will receive rituximab, and fludarabine and cyclophosphamide conditioning chemotherapy, followed by axicabtagene ciloleucel and additional rituximab.
Intervention Type
Biological
Intervention Name(s)
Axicabtagene Ciloleucel
Other Intervention Name(s)
Yescarta®
Intervention Description
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
RITUXAN®
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Administered according to package insert
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Administered according to package insert
Primary Outcome Measure Information:
Title
Complete Response (CR) Rate
Description
CR rate is defined as the incidence of a CR per the Lugano Classification as determined by study investigators.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Percentage of Participants Experiencing Adverse Events and Clinically Significant Changes in Safety Lab Values
Time Frame
Up to 15 years
Title
Objective Response Rate (ORR)
Description
ORR is defined as the incidence of either a CR or a partial response (PR) per the Lugano Classification as determined by study investigators.
Time Frame
Time Frame: Up to 2 years
Title
Duration of Response (DOR)
Description
DOR is defined only for participants who experience an objective response and is the time from the first objective response to disease progression per the Lugano Classification as determined by study investigators or death from any cause.
Time Frame
Up to 2 years
Title
Progression-Free Survival (PFS)
Description
PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano Classification as determined by study investigators or death from any cause.
Time Frame
Up to 2 years
Title
Overall Survival (OS)
Description
OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
Time Frame
Up to 15 years
Title
Levels of Axicabtagene Ciloleucel in Blood
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Histologically confirmed large B-cell lymphoma Chemotherapy-refractory disease, defined as one or more of the following: No response to first-line therapy (primary refractory disease) No response to second or greater lines of therapy OR Refractory after autologous stem cell transplant (ASCT) At least 1 measureable lesion according to the Lugano Classification (Cheson 2014). Individuals must have received adequate prior therapy, including at a minimum: Anti-CD20 monoclonal antibody An anthracycline-containing chemotherapy regimen Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate renal, hepatic, pulmonary, and cardiac function Key Exclusion Criteria: Known CD19 negative or CD20 negative tumor History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL) Prior CAR therapy or other genetically modified T-cell therapy Prior organ transplantation including prior allogeneic stem cell transplant (SCT) Prior CD19 targeted therapy Clinically significant infection or cardiopulmonary disease Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed) History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases History of autoimmune disease History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kite Study Director
Organizational Affiliation
Kite, A Gilead Company
Official's Role
Study Director
Facility Information:
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3012
Country
United States
Facility Name
Stanford Cancer Institute
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
UCLA Hematology/Oncology
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Mayo Clinic Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
John Theurer Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Columbia University Medical Center, New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
St. David's South Austin Medical Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78704
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy/
IPD Sharing Time Frame
18 months after study completion
IPD Sharing Access Criteria
A secured external environment with username, password, and RSA code.
IPD Sharing URL
https://www.gileadclinicaltrials.com/transparency-policy/
Citations:
PubMed Identifier
34515338
Citation
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
Results Reference
derived
Links:
URL
https://www.gileadclinicaltrials.com/study/?id=KT-US-471-0114
Description
Gilead Clinical Trials Website

Learn more about this trial

Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma

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